Phase I clinical trials are the culmination of the costly and laborious preclinical screening process and are the foundation for studies of human antitumor activity. The University of Wisconsin has had continuous NCI funding for its phase I studies since 1979. This proposal details our extensive experience in conducting phase I trials and outlines our goals for continuation of such work as detailed in our specific aims: [unreadable] Aim 1: Determination of Dose Limiting Toxicity and Maximum Tolerated Dose in Early Phase Trials [unreadable] Aim 2: Definition of Pharmacokinetic and Pharmacodynamic Endpoints in Phase I Clinical Trials [unreadable] Aim 3: Molecular Target Assessment in the Determination of Drug Mechanisms, Biologic Endpoints, and Response [unreadable] Aim 4: New Designs and Paradigms for the Evaluation of Novel Agents [unreadable] [unreadable] [unreadable]